title: Extracellular acidic pH inhibits oligodendrocyte precursor viability, migration, and differentiation.
abstract: Axon remyelination in the central nervous system requires oligodendrocytes that produce myelin. Failure of this repair process is characteristic of neurodegeneration in demyelinating diseases such as multiple sclerosis, and it remains unclear how the lesion microenvironment contributes to decreased remyelination potential of oligodendrocytes. Here, we show that acidic extracellular pH, which is characteristic of demyelinating lesions, decreases the migration, proliferation, and survival of oligodendrocyte precursor cells (OPCs), and reduces their differentiation into oligodendrocytes. Further, OPCs exhibit directional migration along pH gradients toward acidic pH. These in vitro findings support a possible in vivo scenario whereby pH gradients attract OPCs toward acidic lesions, but resulting reduction in OPC survival and motility in acid decreases progress toward demyelinated axons and is further compounded by decreased differentiation into myelin-producing oligodendrocytes. As these processes are integral to OPC response to nerve demyelination, our results suggest that lesion acidity could contribute to decreased remyelination.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Jagielska
authors.forename: Kristen D
authors.initials: KD
authors.lastname: Wilhite
authors.forename: Krystyn J
authors.initials: KJ
authors.lastname: Van Vliet
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D003711:Demyelinating Diseases / Q000503:physiopathology*; D045604:Extracellular Fluid / Q000737:chemistry; D005434:Flow Cytometry; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008853:Microscopy; D009186:Myelin Sheath / Q000737:chemistry / Q000502:physiology*; D058953:Neural Stem Cells / Q000737:chemistry / Q000502:physiology*; D009836:Oligodendroglia / Q000737:chemistry / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley